16-56389295-C-G

Variant names:

• chr16-56389295-C-G
• rs758196891
• NM_001144.6:c.1166G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144.6(AMFR):​c.1166G>C​(p.Arg389Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R389H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMFR NM_001144.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 1 publications found

Genes affected

AMFR (HGNC:463): (autocrine motility factor receptor) This locus encodes a glycosylated transmembrane receptor. Its ligand, autocrine motility factor, is a tumor motility-stimulating protein secreted by tumor cells. The encoded receptor is also a member of the E3 ubiquitin ligase family of proteins. It catalyzes ubiquitination and endoplasmic reticulum-associated degradation of specific proteins. [provided by RefSeq, Feb 2012]

AMFR Gene-Disease associations (from GenCC):

• spastic paraplegia 89, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13785857).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMFR	NM_001144.6	MANE Select	c.1166G>C	p.Arg389Pro	missense	Exon 9 of 14	NP_001135.3
	AMFR	NM_001323512.2		c.1166G>C	p.Arg389Pro	missense	Exon 9 of 15	NP_001310441.1
	AMFR	NM_001323511.2		c.881G>C	p.Arg294Pro	missense	Exon 9 of 14	NP_001310440.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMFR	ENST00000290649.10	TSL:1 MANE Select	c.1166G>C	p.Arg389Pro	missense	Exon 9 of 14	ENSP00000290649.5	Q9UKV5
	AMFR	ENST00000861442.1		c.1166G>C	p.Arg389Pro	missense	Exon 9 of 14	ENSP00000531501.1
	AMFR	ENST00000861443.1		c.1166G>C	p.Arg389Pro	missense	Exon 9 of 14	ENSP00000531502.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.074
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.9
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.057
Sift	Benign	0.14	T
Sift4G	Benign	0.15	T
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.36		Loss of stability (P = 0.0977)
MVP		0.49
MPC		0.74
ClinPred		0.57	D
GERP RS		5.9
Varity_R		0.20
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs758196891; hg19: chr16-56423207;